Our main aim is to test the hypothesis that postherpetic neuralgia (PHN) is associated with persistence of varicella-zoster virus (VZV) in blood mononuclear cells (MNC). The formulation of this hypothesis is based on the view that PHN results from the continued presence of virus in dorsal root ganglion cells after resolution of the skin rash. To test this directly would require obtaining ganglion cells at different periods after zoster infection, and this is not practicable. Our detection of VZV-DNA in MNC from zoster patients provides an alternative approach to test our hypothesis. DNA from blood MNC of zoster patients will be hybridized to VZV-RNA probes. The amount and persistence of VZV will be statistically analyzed in the high- and low-risk postherpetic neuralgia population. Southern blotting, in situ hybridization and immunoprecipitation will be used to identify the cell type(s) in which VZV replicates and/or persists. The virologic studies will be performed in concert with studies of humoral and cell-mediated immune function to VZV in both populations. These viral immunologic studies are distinct, but complementary to those of project III which includes a prospective analysis of VZV immune function in young and elderly individuals without zoster. Finally, an in vitro infection model will be established to study the physical state of viral DNA sequences and their respective products in MNC, and to explore the consequences of virus infection on MNC function. This component of the study is essential to test the subsidiary hypothesis that persistence of the VZV genome alters cell function which is itself immunosuppressive.